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Genetics of C-reactive protein and complement factor H have an epistatic effect on carotid artery compliance: the

J Jylhävä1, C Eklund, T Pessi

  • 1Department of Microbiology and Immunology, Medical School, University of Tampere, Tampere, Finland. juulia.jylhava@uta.fi

Clinical and Experimental Immunology
|December 17, 2008
PubMed

Insights

Gene interactions between C-reactive protein (CRP) and complement factor H (CFH) influence early atherosclerosis. A specific CRP haplotype combined with the CFH Tyr402His polymorphism impacts carotid artery elasticity in males.

Area of Science:

  • Cardiovascular Genetics
  • Immunogenetics
  • Atherosclerosis Research

Background:

  • Atherosclerosis involves inflammation, with C-reactive protein (CRP) potentially modulating complement activity.
  • Complement factor H (CFH) binding is implicated in this process, particularly via the CFH Tyr402His polymorphism.

Purpose of the Study:

  • To investigate gene-gene interactions between CRP haplotypes and the CFH Tyr402His polymorphism.
  • To determine the effect of these interactions on early markers of atherosclerosis, specifically carotid artery compliance (CAC) and intima-media thickness (IMT).

Main Methods:

  • Genotyping of single nucleotide polymorphisms (SNPs) in CFH (Tyr402His) and CRP in 1698 participants (aged 24-39 years) from the Cardiovascular Risk in Young Finns Study.
  • Construction of CRP haplotypes and examination of their interactive effects with the CFH Tyr402His polymorphism on CAC and IMT.
  • Statistical analysis including risk factor adjustment and logistic regression.

Main Results:

  • A significant gene-gene interaction between CRP haplotype ATGTG and the CFH Tyr402His polymorphism was found to affect CAC in males (P=0.007).
  • Logistic regression confirmed this risk-modifying interaction, showing an odds ratio of 3.70 (P=0.010).
  • No significant effects on CAC were observed in females, and no effects on IMT were detected in either sex.

Conclusions:

  • The combined presence of the CRP haplotype ATGTG and the CFH 402His allele may negatively impact carotid artery elasticity in males.
  • These findings highlight sex-specific genetic interactions influencing early vascular changes in atherosclerosis.

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